1 Background

In 2022, the global prevalence of HIV was estimated at 39.9 million, with about 1.3 million new infections, of which 53% were women, accounting for 44% of all new infections. About 60% of people newly infected with HIV lived in sub-Saharan Africa (SSA). Every week, around 5000 young women aged 15–24 years become infected with HIV [1].

Pre-exposure prophylaxis (PrEP), an HIV prevention treatment taken by people who are at risk of getting infected with HIV, has been in use as a strategy to curtail HIV transmission [2]. Since its launch in 2012, PrEP use globally has been demonstrated to be more effective when taken exactly as prescribed, lowering the risk of HIV infection by 27%–99% compared to no PrEP [2-4]. Pharmacological interventions for PrEP can be taken through the vagina, orally or by injection. These include Dapivirine Vaginal Ring (DVR) a short term tool containing Dapivirine treatment inserted through the vagina [3]; Apretude, a long-acting injection with antiretroviral cabotegravir given once every 2 months; Truvada, an oral method combining tenofavir, disoproxil, and emtricitabine; as well as Descovy, an oral method containing tenofovir alafenamide and emtricitabine [4-7].

Although multiple PrEP methods already exist with a high prevention rate against HIV infections when usage instructions are adhered to, new HIV preventative methods are still required to meet the specific needs of women [8]. This is important, especially in settings where women are at a high risk of being violated and in scenarios where they have limited abilities to negotiate for safe sex practices [9]. As a result of this need gap, the DVR was developed to provide women more control over HIV prevention [8]. DVR is viewed as a tool that promotes women's sexual rights because they frequently lack discrete HIV preventive tools, have limited negotiation power with male partners to use condoms, and experience sexual violence, a problem common among women living in disadvantaged situations. DVR can also be used easily without experts' assistance and frequent hospital visit [9].

DVR is a non-nucleoside HIV-1 reverse transcriptase inhibitor that works against a wide range of HIV-1 subtypes. DVR provides cisgender women with a less user-dependent option by releasing the antiretroviral medication Dapivirine once a month with little systemic effects [10, 11]. In phase 1 and 2 trials, the safety and acceptability of this monthly 25 mg product containing DVapivirine were tolerable [5, 12-15]. Similarly, data from phase 3 randomized, double-blind, placebo-controlled trials showed that DVR had a relative risk reduction of 27% in the Aspire study as compared to 31% in the Ring study [10, 16]. Adherence to the ring is often assessed in two or three categories based on the levels of drug delivered (0.9 mg or less [no adherence], more than 0.9–4.0 mg (moderate adherence), and more than 4.0 mg [good adherence]) [3, 16]. In some trials, self-reports after ring utilization were also used to assess adherence [17]. DVR gained approval from the World Health Organization (WHO) in 2021, as well as national licenses, particularly in Africa, to be added to the list of essential pharmaceuticals [11, 18].

At 12 months, both the demand and acceptance rates for DVR—which is defined as the ability to use the ring when it is available and under nearly real-life circumstances, such as visits once every 3 months and less regular HIV testing—were found to be above 70% [12, 17]. Several techniques have been employed to investigate the reasons behind DVR adherence. Findings revealed that factors such as disclosing the use of DVR to a supportive person improved adherence [19, 20]. Studies have shown that women who have healthy sexual discussions with their partners are also likely to adhere to DVR use [21, 22]. Adherence to the ring has been shown to vary from 48% to 80% [14, 23, 24]. Nonetheless, the current literature has reported adherence differences in some ways, often influenced by age groups, geographic locations, and marital status [10, 17]. For instance, a secondary data analysis from a randomized control study suggested that some groups of women, such as sex workers, would find the ring more advantageous [25]. However, there are no pooled estimates of adherence to the DVR [17], limiting the evidence base to guide decision-making and practice [26].

Possible challenges with the use of DVR include adverse events such as urinary tract infection, vaginal discharge, vulvovaginal pruritus (itching), vulvovaginitis, and pelvic pain [27]. Evidence indicates that vaginal bleeding causes some women to remove DVR due to hygienic concerns, beliefs that the ring could block menstrual flow, fears that the ring would come out with blood or during tampon removal, and fear of overburdening the vagina [3, 28]. Nevertheless, some studies showed that the majority (60%) of women aged 18–45 years old did not mind wearing the ring during vaginal bleeding and would not remove it (91%) [28].

Despite these challenges and concerns, the European Medicines Agency, considered them manageable given the presumed benefits and protection DVR provides to women [27]. Strategies to improve ring uptake include working with and training healthcare providers with available guides and friendly counseling techniques to encourage usage; working with nongovernmental organizations and community health workers to ensure that the tool is provided in a culturally sensitive manner while addressing stigma, side effects, and myths about the rings [10].

2 Method

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Protocols checklist was followed to report our study protocol [29]. This protocol is registered with PROSPERO (registration number CRD42024593018). Findings from this study will be reported according to the PRISMA guidelines [30].

3 Discussion

Adherence to DVR remains understudied in Africa [17]. This systematic review and meta-analysis will contribute to a better understanding of how DVR adherence aids in preventing HIV-1 infection in women, as well as the factors that influence observed adherence. Its findings can provide important foundational knowledge for future research and innovation in DVR and other PrEP tools. This is especially relevant because some studies have shown that certain groups of women adhere better than others [10, 17, 25]. Such knowledge might introduce implementation research in other parts of Africa for women with similar risk towards HIV prevention. Additionally, findings might help scale up uptake, especially among women in humanitarian settings where violence rates might increase. Furthermore, understanding the trends of adherence would help us tailor suggestions on strategies to meet the identified specific needs of women, including community outreach towards ring use and adherence. Our findings may also encourage policymakers in Africa to include the DVR in their essential drug packages, particularly in Southern and Eastern Africa, where HIV prevalence is increasing [1].

This review will first be submitted to McMaster University as part of a master's degree program requirement. They will also be published in a peer-reviewed journal and discussed at a conference targeting policymakers.

4 Conclusion

The expected results and impact from this systematic review and meta-analysis on DVR adherence will contribute to improving research and development in HIV prevention tools and scale-up. It is also most importantly expected to informed ongoing efforts to expand access to safe, women-controlled HIV prevention tool in the African continent.

Author Contributions

Roseline Dzekem Dine: conceptualization, writing – original draft, writing – review and editing, methodology. Giulia Muraca: writing – review and editing, methodology. Behnam Sadeghirad: writing – review and editing, methodology. Lawrence Mbuagbaw: writing – review and editing, writing – original draft, conceptualization, supervision, methodology.

Conflicts of Interest

The authors declare no conflicts of interest.

Transparency Statement

The lead author Roseline Dzekem Dine affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.